Fused heterocyclic ring derivative and use thereof

Abstract

The present invention provides a fused heterocycle derivative having a strong Smo inhibitory activity, and use thereof. Specially, the present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or salt thereof, and a medicament containing the compound or a prodrug thereof, which is an Smo inhibitor or an agent for the prophylaxis or treatment of cancer.

The invention claimed is: 
     
       1. A compound represented by a following formula: 
       
         
           
           
               
               
           
         
         wherein 
         X C  is NR C1 , wherein R C1  is methyl; 
         R C2  is a carbamoyl group having 1 or 2 substituents selected from the group consisting of
 (1) a 4- to 7-membered non-aromatic heterocyclic group containing 1 to 4 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom, optionally having from 1 to 3 substituents selected from the group consisting of
 (a) a C 1-6  alkyl-carbonyl group optionally having from 1 to 3 hydroxy groups, and 
 (b) an oxo group; 
 
 (2) a C 3-8  cycloalkyl group optionally having from 1 to 3 substituents selected from the group consisting of
 (a) a hydroxy group, 
 (b) a C 1-6  alkyl group optionally having from 1 to 3 hydroxy groups, 
 (c) a carbamoyl group, 
 (d) a cyano group, 
 (e) a C 2-6  alkynyl group, and 
 (f) a 5-membered aromatic heterocyclic group; 
 
 (3) a C 1-6  alkyl group having one substituent selected from the group consisting of
 (a) an amino group having 1 or 2 C 1-6  alkyl groups optionally having from 1 to 3 hydroxy groups, 
 (b) a C 6-10  aryl group optionally having from 1 to 3 C 1-6  alkylsulfonyl groups, 
 (c) a 4- to 7-membered non-aromatic heterocyclic group containing 1 to 4 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom optionally having from 1 to 3 oxo groups, 
 (d) a 5-membered aromatic heterocyclic group, 
 (e) a hydroxy group, and 
 (f) a C 1-6  alkoxy group; 
 
 (4) a C 6-10  aryl group optionally having from 1 to 3 halogen atoms; 
 (5) a 5- to 6-membered aromatic heterocyclic group; and 
 (6) a C 2-6  alkynyl group; 
 
         R C3  is a C 1-6  alkoxy group optionally having from 1 to 3 halogen atoms; 
         R C5  is a C 6-10  aryl group optionally having from 1 to 3 substituents selected from the group consisting of
 (a) a halogen atom, 
 (b) a C 1-6  alkyl group optionally having from 1 to 3 halogen atoms, and 
 (c) a C 1-6  alkoxy group 
 
         R C6  is a C 1-6  alkyl group; and 
         R C7  is a hydrogen atom, 
         or a salt thereof. 
       
     
     
       2. 6-Ethyl-5-(4-fluorophenyl)-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-3-(2,2,2-trifluoroethoxy)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide or a salt thereof. 
     
     
       3. 6-Ethyl-5-(4-fluorophenyl)-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-3-(1-methylethoxy)-4-oxo-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide or a salt thereof. 
     
     
       4. 3-Ethoxy-6-ethyl-5-(4-fluorophenyl)-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide or a salt thereof. 
     
     
       5. A pharmaceutical composition comprising the compound or salt of  claim 1  and at least one pharmacologically acceptable carrier. 
     
     
       6. The pharmaceutical composition of  claim 5 , which is an Smo inhibitor. 
     
     
       7. A pharmaceutical composition comprising the compound or salt of  claim 2  and at least one pharmacologically acceptable carrier. 
     
     
       8. A pharmaceutical composition comprising the compound or salt of  claim 3  and at least one pharmacologically acceptable carrier. 
     
     
       9. A pharmaceutical composition comprising the compound or salt of  claim 4  and at least one pharmacologically acceptable carrier.